Quantitative in vivo and in vitro clonogenic assays will be used to examine the cytotoxic effects of 1) specific chemotherapeutic agents, such as anthracycline fractionation; 2) the interaction of radiation and chemotherapeutic agents, specifically x-radiation plus 5-fluorouracil or actinomycin D; 3) the interaction of chemotherapeutic agents, specifically cytosine arabinoside plus anthracyclines, 5-fluorouracil plus alkylating agents and chclophosphamide plus BCNU. AKR and L1210 leukemias, Lewis lung carcinoma and normal hematopoietic stewm cells will be studied. Parameters of dose, sequence and interval will be examined in order to optimize cytotoxicity. Flow microfluorometry will be employed in order to define any cellular basis for the interactions noted by the clonogenic assays. Biochemical studies will be done examining drug uptake, drug metabolism and alkaline gradient elution to define extent and kinetics of DNA damage and repair following x-radiation or alkylating agent exposure and any modification by chemotherapeutic agents.